Studies on the pathogenesis of monkey pox. II. Dose-response and virus dispersion.
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Five callitrichids (three common marmosets -Callithrix jacchus -, a black tufted-eared marmoset -C. penicillata-, and a saddle-back tamarin -Saguinus fuscicollis) were diagnosed with islet hyperplasia by histopathology and immunohistochemistry. All were privately-owned, unrelated callitrichids ranging from 2- to 4-year-old. Relevant findings were anorexia (3/5), vomiting (2/5), ptyalism (1/5), polyuria/polydipsia (1/5), respiratory distress (1/5), hyperglycemia (2/3) and glycosuria (1/1); hyperglycemia and glycosuria were associated with pregnancy in a common marmoset and resolved after reducing simple carbohydrates in diet. All five animals died, three of them after few premonitory signs; in two cases, other concurrent diseases unrelated to islet hyperplasia were considered the cause of death. Additional animals from two facilities had high weight (4), physical obesity (3), polyuria/polydipsia/polyphagia/uriposia (1), hyperglycemia (1), and/or glycosuria (2). Pathologic findings in the deceased callitrichids were: islet hyperplasia (5/5); hemosiderosis (5/5); lipomatosis (4/5) of several tissues (atria, 3/5; pancreas, gall bladder, intestine, esophagus, and thyroid, 2/5; liver, 1/5); pancreatic necrosis or steatonecrosis, and/or acute pancreatitis (3/5); and vacuolation of hepatocytes and renal tubular cells most likely consistent with hepatorenal lipidosis (2/5). The islets of Langerhans were more numerous and larger than in a control, and morphologically normal in all cases, except in a common marmoset that had a few cells with a foamy cytoplasm and shrunken hyperchromatic or picknotic nucleus. Insulin (5/5), glucagon (3/5), and somatostatin (3/5) immunohistochemistry revealed that most cells stained positively for insulin diffusely in their cytoplasm (5/5) (staining restricted to the vascular pole of b-cells in the control). These findings suggest that obesity, insulin resistance and/or type II diabetes may be implicated and thus a prospective study on these diseases in callitrichids is necessary to determine their etiopathogenesis.
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BACKGROUND: We explored the possibility of using normal adult rhesus macaques for the preclinical assessment of safety, immunogenicity, and efficacy of newly developed vaccines against Streptococcus pneumoniae infection of the lung. METHODS: Our primary objective was to determine whether an intra-bronchial inoculum of at least 10(6)S. pneumoniae colony-forming units, or one as high as 10(8)-10(9) organisms, could detectably survive in rhesus macaques for a period longer than 1-2 weeks. If so, we hypothesized, it would be possible to observe signs of pneumonia commonly observed in humans, and discriminate between vaccinated/protected animals and controls. Infection was detectable in bronchoalveolar lavage fluids 3-5 weeks post-inoculation. RESULTS: The clinical course of disease mimicked aspects of that of human pneumococcal pneumonia. Signs of inflammation typical of the disease in humans, such as elevated concentrations of neutrophils and of pro-inflammatory cytokines in bronchoalveolar lavage fluids were also observed. CONCLUSIONS: These findings underscore the utility of this model to assess the safety, immunogenicity, and efficacy of newly developed S. pneumoniae vaccines.
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Normal ranges for gamma glutamyl transferase (GGT) in chimpanzees were determined and categorized according to age and sex. Enzyme patterns presented for 36 cases of non-A, non-B (NANB) hepatitis and compared to others with hepatitis A and/or B show that the response of this enzyme to these viral agents in chimpanzees is comparable to that seen in human patients. The value of GGT determinations, in addition to aspartate aminotransferase and alanine aminotransferase for the differentiation of various types of viral hepatitis, is described.
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Free-ranging Old World primates released on St. Catherine's Island, Georgia (USA), were tested for infection with Trypanosoma cruzi as part of a study of the epizootiology of sylvatic T. cruzi in the southeastern USA. The parasite was observed in liver infusion tryptose medium cultures of blood from seven of 11 lion-tailed macaques (Macaca silenus) and one of 19 ring-tailed lemurs (Lemur catta). Cultures of blood from 10 black and white ruffed lemurs (Varecia variegata) were all negative. Analysis of small subunit ribosomal RNA gene polymorphisms detected using polymerase chain reaction techniques indicates that the parasites isolated from both the lion-tailed macaques and the ring-tailed lemur are probably the same as T. cruzi parasites isolated from raccoons (Procyon lotor) trapped on St. Catherine's Island and other locations in the southeastern USA. Foraging lion-tailed macaques were observed to handle and partially consume specimens of Triatoma sanguisuga, the triatomine bug thought to be a vector of T. cruzi in the southeastern USA. Oral transmission of the parasite may have occurred as a result of this behavior.
A disease characterized by edema, proteinuria, hypoproteinemia and hypertension was seen in late gestation in patas monkeys. The initial sign was edema of the perineum, ankles and lower trunk. The onset was abrupt, occurring 7 days or less prepartum. The affected animals were not depressed, and convulsions were not seen. In 6 of the 98 pregnancies during a 1-year period, symptoms of the disease were present. The highest incidence was manifested by primiparous animals with 3 of 36 pregnancies affected. Two of 38 second pregnancies and 1 of 24 third pregnancies were also affected. Five of the animals recovered spontaneously and were normal 14 days postpartum. Edema persisted for 30 days in one female. This animal continued to be hypertensive and had persistent mild proteinuria and hypoproteinemia. She was killed approximately 1 year postpartum due to severe renal disease. The spontaneous disease seen in patas monkeys resembled toxemia of pregnancy in humans more closely than the experimentally induced disease in other animals.
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A lack of social support is associated with increased risk of coronary heart disease morbidity and mortality in human beings. Similarly, chronic social separation (single cage housing) potentiates atherosclerosis in female monkeys. Under the hypothesis that autonomic arousal and/or ovarian impairment may mediate this effect (as both are associated with increased atherosclerosis), heart rate and luteal phase plasma progesterone concentrations were measured in 12 female cynomolgus monkeys that were first socially housed, then individually housed, and finally returned to their original social groups. Afternoon heart rates increased during social separation compared to the social groupings (P < 0.001). Increased heart rates could not be explained by activity levels, which were lower during social separation than in social groupings (P < 0.001). Ovarian function (i.e. luteal-phase progesterone concentrations) was not influenced by housing condition. Single caging reduced the extent of social signaling, even though animals were in visual and auditory contact. Rates of affiliative behaviors increased and time spent alone decreased in post-reunion social groups compared to pre-separation social groups (P's < 0.01). The results indicate that chronic social separation in this group-living species may exacerbate atherosclerosis via altered autonomic activity, as evidenced by higher heart rates during social separation.
The literature dealing with mammary cancer and the presence of the identifiable preneoplastic lesions in the mammary gland of several species has been reviewed. A discrete morphologically identifiable lesion with a high malignant potential is considered preneoplastic. Lobuloalveolar lesions have been identified in the human mammary gland which fit most of the criteria for preneoplasia. The lesions, hyperplastic atypical lobules, are multicentric, have a high statistical association with breast cancer and demonstrate a morphological progression through dysplasia to frank carcinoma. Other breast lesions have a high statistical association but no morphological progression can be seen and their neoplastic potential remains unknown. The significance of these correlations is enhanced by the occurrence of homologous breast lesions in outbred and inbred animal models. Statistical correlation with breast cancer and aberrant morphology has been accepted as presumptive evidence of preneoplasia in some animals. Definitive proof of the neoplastic potential has been obtained in rodent models by transplantation of the suspected lesions and their subsequent development into cancers. Although a strong morphological and statistical analogy exists between the human and animal models, the causes and biological potential of the human lesions await experimental proof.